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. 2019 Apr 1;125(7):1091-1100.
doi: 10.1002/cncr.31885. Epub 2018 Dec 6.

Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes

Prajwal C Boddu  1 , Tapan M Kadia  1 , Guillermo Garcia-Manero  1 , Jorge Cortes  1 , Mansour Alfayez  1 , Gautam Borthakur  1 , Marina Konopleva  1 , Elias J Jabbour  1 , Naval G Daver  1 , Courtney D DiNardo  1 , Kiran Naqvi  1 , Musa Yilmaz  1 , Nicholas J Short  1 , Sherry Pierce  1 , Hagop M Kantarjian  1 , Farhad Ravandi  1
Affiliations

Validation of the 2017 European LeukemiaNet classification for acute myeloid leukemia with NPM1 and FLT3-internal tandem duplication genotypes

Prajwal C Boddu et al. Cancer. .

Abstract

Background: The revised 2017 European LeukemiaNet (ELN) classification (ELN-2017) of acute myeloid leukemia (AML) divides patients into 3 prognostic risk categories, with additional factors such as the fms-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) allele ratio (AR) considered for risk stratification. To the best of the authors' knowledge, the prognostic usefulness of ELN-2017 in comparison with ELN-2010 in younger patients with AML has not been validated to date.

Methods: The authors performed a retrospective study on patients aged <60 years who received idarubicin plus cytarabine (IA)-based induction chemotherapy for newly diagnosed AML.

Results: According to ELN-2017 criteria, the number of patients in the favorable (Fav), intermediate (Int), and adverse (Adv) risk categories was 192 patients (27%), 331 patients (46%), and 192 patients (27%), respectively. Overall survival probabilities at 5 years in the Fav, Int, and Adv groups were 57%, 37%, and 18%, respectively. In comparison, the 5-year overall survival probabilities in the Fav (169 patients), intermediate (IR)-1 (80 patients), IR-2 (306 patients), and Adv (160 patients) ELN-2010 categories were 59%, 32%, 40%, and 14%, respectively. Although ELN-2010 historically distinguishes prognosis into IR-1 and IR-2 categories in younger patients, this difference was nullified in the current study cohort. When comparing patients with a low FLT3-ITD AR with those with a high FLT3-ITD AR, no significant differences in survival were noted among patients with nucleophosmin 1 (NPM1)-mutated AML (P = .28) or wild-type NPM1 (P = .35), and in those treated with IA alone (P = .79) or those treated with IA and a FLT3 inhibitor (P = .10).

Conclusions: The ELN-2017 more accurately distinguishes prognosis in patients with newly diagnosed AML. The lack of prognostic significance for the FLT3-ITD AR needs further evaluation in different treatment settings.

Keywords: European LeukemiaNet; acute myeloid leukemia; allele ratio; prognosis; validation; younger.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

Figures

Figure 1.
Figure 1.
Changes in the risk categories between the 2010 European LeukemiaNet (ELN-2010) classification system and the ELN-2017 classification system with the ELN-2017 system.
Figure 2.
Figure 2.
Overall survival according to the 2017 European LeukemiaNet (ELN-2017) classification system and ELN-2010 risk categories (A) overall, irrespective of transplantation status and (B) when censoring for allogeneic stem cell transplantation.
Figure 3.
Figure 3.
Overall survival according to 2010 European LeukemiaNet (ELN-2010) classification subgroups within the ELN-2017 favorable risk category (Fav). IR-2 indicates intermediate II risk.
Figure 4.
Figure 4.
Overall survival according to 2010 European LeukemiaNet (ELN-2010) classification subgroups within the ELN-2017 intermediate risk category (A) overall, irrespective of transplantation status and (B) when censoring for allogeneic stem cell transplantation. IR-1 indicates intermediate I risk; IR-2, intermediate II risk.
Figure 5.
Figure 5.
Overall survival according to 2010 European LeukemiaNet (ELN-2010) classification subgroups within the ELN-2017 adverse risk category (Adv). IR-1 indicates intermediate I risk.
Figure 6.
Figure 6.
Overall survival according to the nucleophosmin 1 (NPM1) and fms-like tyrosine kinase 3 (FLT3) genotypes as per the 2017 European LeukemiaNet (ELN-2017) classification system. FLT3high indicates high FLT3 high allele ratio; FLT3low, low FLT3 allele ratio; mNPM1, NPM1-mutated acute myeloid leukemia; wtNPM1, wild-type NPM1.
See this image and copyright information in PMC

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